Direct compression is a tableting process in which tablets are compressed directly from powder blends containing an active ingredient. In direct compression, all the ingredients required for tableting, including the active ingredient and processing aids, are incorporated into a free flowing blend which is then tableted. The active ingredient, excipients, and other substances are blended and then compressed into tablets. Tablets are typically formed by pressure being applied to a material in a tablet press.
There are a number of tablet presses, each varying in productivity and design but similar in basic function and operation. All compress a tablet formulation within a die cavity by pressure exerted between two steel punches, a lower punch and an upper punch.
Pharmaceutical manufacturers prefer the use of direct compression, over wet and dry granulation processes, because of its shorter processing times and cost advantages. However, direct compression is generally limited to those situations in which the active ingredient has physical characteristics suitable for forming pharmaceutically acceptable tablets.
Some active ingredients, which are generally unsuitable for direct compression, can be formed into a directly compressible formulation by incorporating one or more excipients before compressing. The addition of excipients to the formulation, however, will increase the tablet size of the final product. As tablet size must be within certain parameters to function as a suitable dosage form, there is a limit beyond which increasing tablet size to accommodate increasing amounts of excipients to enhance compactability is not practical. As a result, manufacturers are often limited to using the direct compression method for formulations containing a low dose of the active ingredient per compressed tablet such that the formulation may accommodate sufficient levels of excipient to make direct compression practical.
In the development of pharmaceutical dosage forms, it is important to balance several different objectives. Preparation of a pharmaceutical dosage form should be economical. Also, the dosage form should be easy to swallow. Further, smaller dosage forms are more acceptable to patients and result in improved patient compliance.
It is known that, to form a tablet from a given formulation, the formulation must have good flow properties for precise volumetric feeding of the material to the die cavity and suitable compressibility, compactability, and ejection properties to form a tablet. The flow properties of powders are critical for efficient tableting operation. The ability of the material to flow freely into the die is important to ensure that there is uniform filling of the die and a continuous movement of the material from its source. Poor flow properties of the material will affect the weight, hardness and friability of the tablets. Good flow of powders, to be compressed, is necessary to assure efficient mixing and acceptable weight uniformity for the compressed tablets.
Azithromycin, which is also named 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, generally, is not considered to be amenable to the production of directly compressible tablets of azithromycin formulations.
It would be desirable to develop an azithromycin formulation that is amenable to direct compression and that produces tablets having acceptable hardness and friability.